Next generation metagenomics. Applying the latest scientific advances supports society directly through promoting a knowledge based economy, as well as indirectly through securing agricultural productivity, improved biomedical applications and a greater understanding of our changing environment. Establishing these methods places Australia at the forefront of genomics technology with direct applications for Australian biomedical and biotechnology industries. Applying next generation sequencing fo ....Next generation metagenomics. Applying the latest scientific advances supports society directly through promoting a knowledge based economy, as well as indirectly through securing agricultural productivity, improved biomedical applications and a greater understanding of our changing environment. Establishing these methods places Australia at the forefront of genomics technology with direct applications for Australian biomedical and biotechnology industries. Applying next generation sequencing for metagenomics will provide a detailed understanding of microbial population structures and lead to advances in biomedicine, agriculture and environmental science. Read moreRead less
Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identifie ....Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identified a new genetic system, the 'phasevarion', that mediates random expression of multiple genes. The proposed research aims to advance our understanding of gene expression at the most basic level, revealing how bacteria generate diverse populations to evade environmental and immune stresses, and facilitating improved interpretation and use of DNA sequences for researchers and industry in this field.Read moreRead less
Safety in numbers: Bacterial aggregation and adaptation to oxidative stress. This project is a new collaboration which links two molecular microbiologists with the complementary skills required to make new insights into the molecular processes that underpin bacterial aggregation and biofilm formation. Biofilms are of immense significance in medical, industrial and environmental settings and so the fundamental information gained from this project will have wider relevance to the field of microbio ....Safety in numbers: Bacterial aggregation and adaptation to oxidative stress. This project is a new collaboration which links two molecular microbiologists with the complementary skills required to make new insights into the molecular processes that underpin bacterial aggregation and biofilm formation. Biofilms are of immense significance in medical, industrial and environmental settings and so the fundamental information gained from this project will have wider relevance to the field of microbiology. An outcome of this proposal will be fundamental knowledge about the production of surface adhesins that will form the basis for rational treatment of disease in the future. Prevention of aggregation and biofilm formation would make bacterial populations more susceptible to conventional antibiotic treatment.Read moreRead less
Molecular mechanisms of pilin glycosylation in Neisseria: a model system for protein glycosylation in bacteria. The disease causing bacteria Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens. Cell surface structures, called pili, are known to be important in allowing the bacteria to stick to host cells. Genetic and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. Until recently ....Molecular mechanisms of pilin glycosylation in Neisseria: a model system for protein glycosylation in bacteria. The disease causing bacteria Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens. Cell surface structures, called pili, are known to be important in allowing the bacteria to stick to host cells. Genetic and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. Until recently glycosylation of Gram-negative bacterial proteins was not thought to occur, however our recent work with these bacteria, and other groups studying Pseudomonas and Campylobacter, have shown that this process may be widespread. In our previous studies, we have identified and analysed a number of genes involved in pili glycosylation, in bacteria, which make known sugar structures. We have used this information to developed models for how the biochemistry and physiology of the glycosylation system may work. With a well-established structure and many genes already identified, glycosylation in Neisseria represents the best available model system to study this novel and important process. In the proposed study we describe experiments planned to test our models and reveal the molecular detail of this process. This study could lead to major advances in our understanding of this process and, when understood, may have future applications in biotechnology.Read moreRead less
The only constant is change: ecology and evolution of phage-host interactions in a model ecosystem. Microorganisms underpin life on Earth, but our understanding of their diversity and activity is limited by our inability to grow most of them in the laboratory. Recently, new techniques have emerged that allow access to the genetic information of all microorganisms by directly sequencing DNA and RNA from the environment. In this research we will further develop these frontier technologies, promoti ....The only constant is change: ecology and evolution of phage-host interactions in a model ecosystem. Microorganisms underpin life on Earth, but our understanding of their diversity and activity is limited by our inability to grow most of them in the laboratory. Recently, new techniques have emerged that allow access to the genetic information of all microorganisms by directly sequencing DNA and RNA from the environment. In this research we will further develop these frontier technologies, promoting this new area of science in Australia. We will apply these techniques to microbial communities involved in wastewater treatment in order to understand the interactions between microorganisms and the viruses that infect them. Understanding this interaction will have important implications for optimising these treatment processes.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180101563
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
The sweet road to synthesis of bacterial sugar structures. This project aims to characterise the synthesis pathways of nonulosonic acid sugars (NulOs) in bacteria using a combination of bioinformatics and experimental methodologies. Bacteria produce long chains of sugars or glycans on their cell surface known as capsules. These often contain important NulOs that can be uniquely harvested for use in the nutrition, cosmetic and bioremediation industries. By understanding the natural pathways of th ....The sweet road to synthesis of bacterial sugar structures. This project aims to characterise the synthesis pathways of nonulosonic acid sugars (NulOs) in bacteria using a combination of bioinformatics and experimental methodologies. Bacteria produce long chains of sugars or glycans on their cell surface known as capsules. These often contain important NulOs that can be uniquely harvested for use in the nutrition, cosmetic and bioremediation industries. By understanding the natural pathways of their synthesis, ‘glycans-by-design’ can be synthetically created with potent tailor-made properties. This project endeavours to examine how glycans with acidic sugars are produced to generate a fundamental understanding of sugar biology and create a database that will advance industrial applications in glycoengineering.Read moreRead less
Autotransporter proteins of Escherichia coli. Autoransporters are a novel class of proteins associated with bacterial virulence properties such as adhesion, invasion and biofilm formation. Despite this, limited information is available on their functional role. The aim of this project is to characterize several of the autotransporter proteins from pathogenic E. coli. The likely contribution of these proteins to infection suggests that they are potential targets for strain attenuation and vaccine ....Autotransporter proteins of Escherichia coli. Autoransporters are a novel class of proteins associated with bacterial virulence properties such as adhesion, invasion and biofilm formation. Despite this, limited information is available on their functional role. The aim of this project is to characterize several of the autotransporter proteins from pathogenic E. coli. The likely contribution of these proteins to infection suggests that they are potential targets for strain attenuation and vaccine strain construction. Many of these proteins also mediate bacterial aggregation and are therefore targets for novel drugs that inhibit this process. The project will be carried out with a high profile partner from Denmark and will provide opportunity for travel and technology development. Read moreRead less
Evolution of bacterial pathogenesis. Little is known regarding the specific evolutionary steps involved in the emergence of highly virulent microbial pathogens from benign or mildly virulent populations. The group A streptococcus is exemplary of this vexing problem - a large population reservoir of bacteria exists causing only mild infections and a highly virulent strain emerges causing significant disease and mortality. Utilising an extensive WHO reference collection of group A streptococcus is ....Evolution of bacterial pathogenesis. Little is known regarding the specific evolutionary steps involved in the emergence of highly virulent microbial pathogens from benign or mildly virulent populations. The group A streptococcus is exemplary of this vexing problem - a large population reservoir of bacteria exists causing only mild infections and a highly virulent strain emerges causing significant disease and mortality. Utilising an extensive WHO reference collection of group A streptococcus isolates. This project will define the evolutionary events that produced the most significant invasive strain designated M1T1. The M1T1 strain emerged in the mid-1980s, has since disseminated globally, yet the evolutionary sequence of events resulting in this emergence are largely unknown.Read moreRead less
Autotransporter proteins of enterohemorrhagic Escherichia coli O157:H7. Escherichi (E.) coli O157:H7 has caused hundreds of outbreaks in the United States and United Kingdom. Although not currently a major problem in Australia, the emergence of E. coli O157:H7 here would have serious implications for our meat and livestock industry. This study will provide important information for the selection of vaccine antigens used to prevent the colonisation of cattle with E. coli O157:H7 and other diarrho ....Autotransporter proteins of enterohemorrhagic Escherichia coli O157:H7. Escherichi (E.) coli O157:H7 has caused hundreds of outbreaks in the United States and United Kingdom. Although not currently a major problem in Australia, the emergence of E. coli O157:H7 here would have serious implications for our meat and livestock industry. This study will provide important information for the selection of vaccine antigens used to prevent the colonisation of cattle with E. coli O157:H7 and other diarrhoeagenic E. coli serotypes. A direct outcome of this will be improved human health, as E. coli O157:H7 can cause life threatening infections in humans. The study will also examine the contribution of specific adhesins to biofilm formation; measures to prevent biofilm formation may reduce the persistence and spread of E. coli O157:H7 in the environment.Read moreRead less
Epigenetic regulation in bacteria. This project aims to understand the effect of DNA modification on gene regulation in the bacterial organism Escherichia coli, which causes urinary tract infection worldwide. High-throughput DNA sequencing technologies mean one can determine the entire genetic blueprint of a bacterium – its genome – accurately, quickly and cheaply. Single-molecule real-time sequencing provides a complete read-out of a bacterial genome (genetic data) and chemical modifications of ....Epigenetic regulation in bacteria. This project aims to understand the effect of DNA modification on gene regulation in the bacterial organism Escherichia coli, which causes urinary tract infection worldwide. High-throughput DNA sequencing technologies mean one can determine the entire genetic blueprint of a bacterium – its genome – accurately, quickly and cheaply. Single-molecule real-time sequencing provides a complete read-out of a bacterial genome (genetic data) and chemical modifications of the DNA (epigenetic data). Epigenetic data can affect regulation: how genes are switched off and on. This project seeks to harness the power of single-molecule DNA sequencing, together with state-of-the-art genomic and molecular approaches, to better understand the impact of DNA modification on gene regulation in the model bacterial organism, Escherichia coli. This work will support advanced training in bioinformatics and microbiology and improve our understanding of regulation in all bacteria.Read moreRead less